The incidence of myocardial infarction is related to the extent to which arteries are occluded by blood clots (thrombi). Platelet, cells that aggregate in response to arterial injury, are the major cellular components found in such thrombi. Thrombolytic therapies (which do not affect platelet) are effective in removing clots but do prevent platelet-dependent reocclusion and can cause hemorrhage, which requires platelet adhesion. Platelet aggregation is mediated by cell surface glycoprotein (GP) IIb/IIa complex, which recognize the Arg-Gly-Asp (RGD) sequence found in plasma adhesive proteins such as fibrinogen and von Willebrand factor. RGD-containing peptide analogues will be screened for their superior inhibitory effects against platelet aggregation as well as for increased specificity for the GP IIp/IIa receptor. Also, the RGD-dependent interactions of GP IIb/IIa with major adhesive proteins will be assessed via the attachment of liposomes containing the purified receptor. Peptide exhibiting high antagonistic potencies against these responses will also be test for their undesirable effects on the release of vasoconstrictory and chemotactic substances form platelet and on endothelial cell activation and detachment. Finally, the anti-thrombotic efficacies of candidate peptide will be determined in several animal models of thrombosis. It is hoped that this research will lead to a product(s) with actions synergistic to those of conventional thrombolytic therapies.